1. Field of the Invention
The invention relates to soft capsules coated with an enteric coating without need for a subcoating and optionally additionally coated with a protective coating and method of preparation thereof.
2. Information Disclosure Statement
Enteric coating of soft capsules has heretofore required a glidant such as talc to prevent agglomeration of the capsules and a subcoating to stiffen the capsules and thereby prevent distortion thereof during coating. The prior art does not describe or suggest any means of overcoming either problem. The presently described and claimed invention overcomes both of them.
A Rohm Pharma product brochure entitled "Eudragit L 30 D--Aqueous Acrylic Resin Dispersion--Application in the Production of Pharmaceutical Preparations" (Info LD-1/e, pages 1-7 and Info LD-2/e, two pages) describes EUDRAGIT L 30 D and use thereof as follows:
EUDRAGIT L 30 D is utilised predominantly for covering orally administered pharmaceutical dosage forms, particularly tablets, pills and capsules, with coatings which are resistant to gastric juice but soluble in intestinal juice.
EUDRAGIT L 30 D is a copolymer, anionic in character, based on polymethylacrylic acid and acrylic acid esters.
The ratio of the free carboxyl groups to the ester groups is 1:1.
The mean molecular weight is 250 000.
EUDRAGIT L 30 D is supplied as an aqueous dispersion containing 30% w/w of dry lacquer substance.
To achieve coatings which are resistant to gastric juice, it is necessary to apply lacquer containing 3 to 6 mg of dry substance per sq. cm of tablet surface. For enteric coatings with delayed drug release in the intestine, larger quantities of lacquer will possibly need to be applied. In certain cases, EUDRAGIT L 30 D containing 30% w/w of dry lacquer substance can be employed undiluted, possibly for granulation purposes, to isolate porous cores or in fraction application.
Uniform and smooth film coatings are obtained by spray application; this process requires that the dispersion be diluted to some 20% w/w with water. To enhance the elasticity of the EUDRAGIT L 30 D films, the addition of plasticisers is strongly recommended. Polyethylene glycols, propylene glycol, triacetin and dibutyl phthalate, citric acid esters have proved suitable as plasticisers. The addition of 10% w/w of plasticiser, calculated on the dry lacquer substance content, is generally adequate. Where required, this can be increased to 20-25% without adversely affecting the specific solubility characteristics of the lacquer film. The addition of a small quantity of talc reduces the tendency of EUDRAGIT L 30 D to agglutinate during the application process and helps to make the surface of the film smooth. Belanger et al. U.S. Pat. No. 5,047,258, which issued Sep. 10, 1991, describes
[a] method of preventing pharmaceutical dosage forms from adhering during spray coating, comprising: spraying said pharmaceutical dosage forms in the absence of glidant [especially talc] with a mixture consisting essentially of a one to one copolymer of ethyl acrylate and methacrylic acid and a plasticizer in air having an inlet dew point below about 10.degree. C. and an inlet temperature between about 35.degree. C. and about 60.degree. C. PA1 a subcoating composition consisting essentially of hydroxypropyl methyl cellulose about 4%-9%, polyethylene glycol about 0.5%-1% with the remainder water in an [a]mount sufficient to increase the total weight of said shell by about 8%-10%, and thereafter applying one or more continuous coating layers to said shell comprising a known hard tablet coating composition selected from the group consisting of: waterproofing and sealing compounds, smoothing compounds, coloring and finishing compounds, polishing compounds, cellulose polymer film compositions, compression coating compositions, and enteric coating compounds, wherein said subcoating is applied to said capsule shell using standard spraying techniques at a temperature below the distortion temperature of the capsule shell thereby essentially eliminating deformation of the capsule shell during the manufacturing process and capsules prepared by the process. The preferred enteric coating composition is 12-18% of polyvinyl acetate phthalate, 0.25-0.35% concentrated ammonium hydroxide and water to make 100%.
The term "pharmaceutical dosage forms" is not explicitly defined. The specification states that the invention relates to a process for the spray-coating of "tablets, pills, and the like" and illustrates the invention only by tablets in the examples.
Matthews et al. U.S. Pat. No. 4,816,259, which issued Mar. 28, 1989, describes a process for making coated soft gelatin capsules including enteric coated soft gelatin capsules comprising first coating the capsule shell with